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Objective: The objective of this study is to investigate the association between the serum sclerostin, the coronary artery calcification (CAC), and patient outcomes in maintenance dialysis patients. Methods: We performed a prospective cohort study of 65 maintenance dialysis patients in 2014, including 39 patients on peritoneal dialysis and 26 on hemodialysis, and followed up for 5 years. Parameters of mineral metabolism including bone-specific alkaline phosphatase, fibroblast growth factor 23, sclerostin, and other biochemical factors were determined at the baseline. Meanwhile, the CAC score was analyzed by cardiac computed tomography. Results: Serum sclerostin in hemodialysis patients was significantly higher than that in peritoneal dialysis patients (632.35 ± 369.18 vs. 228.85 ± 188.92, p < 0.001). The patients with CAC were older, receiving hemodialysis, lower Kt/V, and had longer dialysis vintage, as well as higher levels of serum 25-(OH)-vit D and sclerostin. In multivariate logistic regression analysis, older age and lower Kt/V were risk factors for CAC. The area under the receiver operating characteristic curves for prediction of CAC by sclerostin was 0.74 (95% confidence interval 0.605–0.878, p = 0.03), and the cutoff value of sclerostin is 217.55 pg/mL with the sensitivity 0.829 and specificity 0.619. After 5 years of follow-up, 51 patients survived. The patients in the survival group had significantly lower age, sclerostin levels, and low CAC scores than the nonsurvival group. Old age (≥60 years, p < 0.001) and high CAC score (≥50 Agatston unit, p = 0.031) were significant risk factors for the patient survival. Conclusions: Sclerostin is significantly elevated in dialysis patients with CAC. But sclerostin is not a risk factor for CAC. After 5 years of follow-up, patients in the survival group are younger and have lower sclerostin levels and CAC scores. But sclerostin levels are not independent risk factors for high mortality in dialysis patients.

The current study aimed to assess the dietary salt intake in patients with CKD in Jiangsu province and investigate the relationship of urinary sodium excretion with blood pressure. A total of 800 patients with CKD stages 1–4 were recruited. All enrolled patients were asked to collect complete 24‐h urine specimen. At the same time, patient's demographic and laboratory data were recorded. The mean age was 47.45 ± 15.25 years old, including 423 men and 377 women. There was no significant difference in urinary sodium excretion among different stages of CKD (p = .748). This study revealed that the median urinary sodium excretion of all patients was 127.20 mmol/d (IQR 91.03–172.06), corresponding to a salt intake of 7.4 g/d. Among them, only 167 (20.9%) cases had salt intake

In recent years, PD-1 immune checkpoint inhibitors based on monoclonal antibodies have revolutionized cancer therapy, but there still exist unresolved issues, such as the high cost, the relatively low response rates, and so on, compared with small-molecule drugs. Herein a type of pyrrole-imidazole (Py-Im) polyamide as a small-molecule DNA binder was designed and synthesized, which could competitively bind to the same double-stranded DNA stretch in the PD-L1 promoter region as the STAT3 binding site and thus downregulate PD-L1 expression. It was demonstrated that the Py-Im polyamides directly caused apoptosis in tumor cells and retarded cell migration in the absence of T cells through inhibiting the Akt/caspase-3 pathway. Also, in a coculture system, they enhanced the T-cell-mediated killing of tumor cells by the reversal of immune escape. Because such polyamides induced antitumor effects via both immune and nonimmune pathways, they could be further developed as promising PD-L1 gene-targeting antitumor drugs.

BACKGROUND Hematopoietic stem cell transplantation (HSCT) is widely used in the treatment of hematological diseases. However, complications after transplantation, such as acute and chronic graft-vs-host disease (GVHD), still seriously affect the quality of life and even threaten the lives of patients. There is evidence that glomerular diseases can manifest as GVHD. However, GVHD should not occur as a result of syngeneic HSCT. CASE SUMMARY A 20-year-old male diagnosed with T lymphoblastic lymphoma (stage IIIA, aaIPI 1) in September 2013 was treated with six cycles of hyper-CVAD and achieved complete remission. He underwent syngeneic HSCT in June 2014, and had no kidney disease history before the transplant. However, nephrotic syndrome occurred 24 mo later in the patient after syngeneic HSCT. Renal biopsy was performed, which led to a diagnosis of atypical membranous nephropathy. After treatment with glucocorticoids combined with cyclophosphamide and cyclosporine, the nephrotic syndrome was completely relieved. CONCLUSION We report a case of delayed nephrotic syndrome after syngeneic HSCT. Antibody-mediated autoimmune glomerular disease may be the underlying mechanism. After treatment with immunosuppressive agents, the nephrotic syndrome was completely relieved but further long-term follow-up is still needed.

Cuticular wax is an important factor that affects storage quality of fruits and vegetables. Previous studies have shown that cuticular wax of pears changes significantly during storage, whereas there are few studies on the effects of different storage methods on the wax changes and the relationship with storage quality. Cuticular wax of Korla pear stored using different methods, was measured to analyze its total wax content, chemical compositions and their relationship with storage quality. At the end of storage, the highest cuticular wax content was observed in controlled atmosphere (CA) storage and the lowest in room temperature storage. The substances of the primary components with higher contents were nonacosane, (E, E)-ɑ-farnesene, dodecan-1-ol, 1,1-dimethoxynonane, nonanal, palmitic acid, and oleic acid. Total wax content, olefins and fatty acids were most significantly with the storage quality, followed by alkanes and esters. Moreover, total wax content, wax composition and weight loss were closely related to postharvest senescence. Overall, an understanding of variations in the cuticular wax under different storage methods could provide theoretical basis for further study on the storage and preservation technology of pears.

We compared the prognostic value of nutritional or volumetric parameters measured by body composition in hospitalized patients on maintenance hemodialysis. We conducted a cohort study to assess the association of different parameters of body composition with all-cause mortality in inpatients admitted to our nephrology department from January 2014 to December 2016. Of the 704 study patients, 160 (22.7%) died during a median follow-up of 33 months. In multivariate adjusted Cox models, higher ratio of extracellular water to body cell mass (ECW/BCM) (adjusted HR per 1-SD, 1.49; 95% CI, 1.19 to 1.85), lower lean tissue index (LTI) (adjusted HR per 1-SD, 0.70; 95% CI, 0.57 to 0.86) and lower body cell mass index (BCMI) (adjusted HR per 1-SD, 0.70; 95% CI, 0.58 to 0.85) were associated with a significantly greater risk of death. When these parameters were added to the fully adjusted model, BCMI performed best in improving the predictability for all-cause mortality (integrated discrimination improvement = 0.02, P = 0.04; net reclassification index = 0.11, P = 0.04). Among body composition indexes, ECW/BCM was the most relevant fluid volume indices to mortality and BCMI and LTI were the most relevant nutritional status indices to mortality in maintenance hemodialysis patients.

Objective To search all available sources to find incontrovertible scientific explanation of the meridian system and mechanism of acupuncture action. Methods Extensive search of electronic databases was carried out to identify all published scientific articles, research papers and experimental findings regarding meridian system, acupuncture points and mechanisms of acupuncture action, from both English and Chinese language journals, from inception till date. Results There are many hypotheses and studies about meridian system such as, primovascular system as meridian, nuclear tracers study to locate the track of meridian, infrared imaging studies to prove existence of meridians, investigations about anatomical structure of acupoints, etc. There are many researches and theories about mechanism of acupuncture action such as gate control theory of acupuncture analgesia, neurotransmitters, neuro-endocrine-immune network, fMRI evidences of brain's processing of pain signal etc. Conclusion Researchers over half a century discovered many factual information about meridian system, acupoints, neuro-transmitters and acupuncture analgesia, neuro-hormonal mechanism etc. All these important discoveries contributed to clarify the mysteries of meridian system and acupuncture action, but they still fell short of providing an incontrovertible scientific explanation. Further coordinated studies are warranted to explore more plausible and scientifically valid explanation of meridian system and acupuncture action.

Uremic cardiomyopathy (UCM) is a common complication in patients with chronic kidney disease (CKD) and an important risk factor for death. P-Cresyl sulfate (PCS) is a damaging factor in UCM, and Klotho is a protective factor. However, the molecular mechanisms of Klotho and PCS in UCM and the relationship between PCS and Klotho are unclear. In vitro, Klotho treatment inhibited PCS-induced cardiomyocyte hypertrophy and apoptosis by blocking mTOR phosphorylation and inhibiting DNA double-strand breaks (DSBs), respectively. Moreover, PCS increased SIRT6 protein ubiquitination and downregulated SIRT6 protein expression, while Klotho inhibited SIRT6 protein ubiquitination and upregulated SIRT6 protein expression. In a mouse model of 5/6 nephrectomy (5/6Nx)-induced UCM, the expression of Klotho in the kidney and serum was decreased, and the expression of SIRT6 protein in myocardial tissues was lower. PCS further reduced Klotho and SIRT6 expression, aggravated heart structure and function abnormalities, and increased myocardial cell apoptosis in UCM mice. Administration of Klotho protein inhibited the downregulation of SIRT6 protein expression and improved cardiac structure and function. Furthermore, serum PCS level was associated with the left ventricular mass (LVM) and left ventricular mass index (LVMI) in hemodialysis patients. In conclusion, the uremic toxin PCS injures cardiomyocytes via mTOR phosphorylation and DSBs, and Klotho antagonizes the damaging effects of PCS. Moreover, the SIRT6 protein plays an important role in UCM, and Klotho suppresses SIRT6 ubiquitination induced by PCS, further improves cardiac structure and function in UCM and exerts protective effects.

Immune checkpoint inhibitors (ICIs) have been more and more commonly used in patients with cancer. Therefore, it is important to understand the immune-related adverse events (irAEs), including immune-related renal adverse events, caused by ICIs. In this article, the authors explore the incidence, clinical features, risk factors and overall outcome of immune checkpoint inhibitor related-acute kidney injury (ICI-AKI) in Chinese patients treated with PD-1 inhibitors for the first time. Among 551 patients treated with PD-1 inhibitors, 65 patients experienced AKI and 31 patients experienced ICI-AKI. Patients with ICI-AKI may be more likely to receive nonsteroidal anti-inflammatory drugs, to receive PD-1 inhibitors for longer cycles or to experience extrarenal immune-related adverse events prior to or concomitant with ICI-AKI. The occurrence of ICI-AKI may not affect the survival time or disease progression of patients with cancer.

Epidermal wax is an important factor affecting the storage quality of fruits and vegetables. Previous studies have shown that the epidermal wax of fruits undergoes significant changes during storage, but there are few studies on the effects of different storage methods on the changes in waxes and the relationship with storage quality. To investigate the effect of cuticular wax on the postharvest physiology in fragrant pear, equal numbers of fragrant pear fruits were stored in room temperature storage (control), cold storage and controlled atmosphere (CA) storage environs, respectively.Gas chromatography-mass spectrometry analysis revealed that the prevailing compositions of cuticular wax of fragrant pear were alkanes, alkenes, alcohols, aldehydes, esters and fatty acids. Compared with the control, cold storage and CA storage significantly inhibited changes in postharvest physiology, total wax contents and wax compositions of fragrant pear, and the effects of CA storage were more pronounced than cold storage. Under different storage methods, total wax contents and wax compositions show different correlations with various physiological indicators.The results obtained in the present study indicate that cold storage and CA storage altered the fragrant pear cuticular wax contents and constituents, thus changing the postharvest physiology quality. The changes in the metabolism of wax components caused by the changes in storage environment mainly affect the changes in the hardness of fragrant pears. The present study provides a theoretical basis for the preservation and storage of fruits. © 2022 Society of Chemical Industry.

The mean perfusion pressure (MPP) was recently proposed to personalized management tissue perfusion pressure in critically ill patients. Increased MPP variability (MPPV) may be associated with organ injuries. Our objective was to determine if increased MPPV was associated with subsequent deterioration of renal function in critically ill patients. We analyzed data stored in the eICU-CRD and MIMIC-IV databases. The exposure was MPPV, measured as the coefficient of variation (CV) using the MPP data of the first 24 h after first ICU admission. The primary endpoint was deterioration of renal function, defined as new-onset or progress of acute kidney injury between 24 and 72 h after ICU admission. The study population consisted of 8,590 patients from eICU-CRD and 6,723 patients from MIMIC-IV database. A total of 28.4% and 30.2% of the study population experienced deteriorated renal function, respectively. Patients with deteriorated renal function had significantly higher median MPP-CV compared with those without (12.2% vs 11.5% and 12.8% vs 12.5%, p < .001). In fully adjusted multivariate logistic models, higher MPP-CV (adjusted OR per 1-SD, 1.08; 95% CI, 1.02–1.13 and adjusted OR per 1-SD, 1.06; 95% CI, 1.00–1.12, respectively) was significantly associated with greater risk of primary endpoint. The pooled analyses showed heterogeneity in patients with cardiac surgery, medical sepsis and others. Increased MPPV was associated with an increased risk of subsequent deterioration of renal function in critically ill patients with central venous pressure monitoring. Maintaining stable MPP may reduce the risk of renal function deterioration.

Continuous renal replacement therapy (CRRT) has become an important multiple organ support therapy and it is widely used in the intensive care unit (ICU). The aim of this study was to clarify the association between CRRT and 28-day mortality in critically ill coronavirus disease 2019 (-COVID-19) patients receiving mechanical ventilation.112 respiratory decompensated critically ill adult patients with COVID-19 admitted to a COVID-19-designated ICU were included in this retrospective cohort study. Data on demographic information, comorbidities, laboratory findings upon ICU admission, and clinical outcomes were collected. The Kaplan-Meier method and Cox proportional hazard model were applied to determine the potential risk factors associated with 28-day mortality.The median age was 65.7 years, 67.8% were males, and 58.9% patients had at least one comorbidity. The median scores of the Charlson Comorbidity Index and Sequential Organ Failure Assessment (SOFA) were 3 and 7, respectively. Acute kidney injury (AKI) occurred in 57 critically ill patients upon ICU admission; 43 patients were classified as stage 2 - 3 AKI, and 36 patients were treated with CRRT. Age 65 years, high SOFA score, damaged cardiac function, poor nutrition, and severe infection were significantly associated with increased 28-day mortality. AKI patients receiving CRRT had lower 28-day mortality compared with those not receiving CRRT (HR = 0.35, 95% CI: 0.21 - 0.58, p 0.001). Initiating CRRT within 72 hours after mechanical ventilation did not improve survival after CRRT initiation.AKI prevalence and 28-day mortality are high in critically ill patients with COVID-19 receiving mechanical ventilation. CRRT plays a part in decreasing the mortality of critically ill COVID-19 patients with AKI receiving mechanical ventilation.

Conventional homeopathy and traditional Chinese medicine (TCM) are two popular alternative systems of medicine, which are practiced also in many countries outsidethe countries of origin. Homeopathy originated in Germany in the 19th century and spread throughout the world in spite of antagonism by theorthodox practitioners. It is a holistic medicine based on the principles of treatment where the remedy and the disease have similar symptoms,applies a single potentized medicine at a time, in minimum dose. TCM, also a holistic medicine originating in ancient China about 3000 years ago, has been developed and practiced through centuries till today as one of the most popular alternative medicines in the world. Both the systems ofmedicine have many differences in theories, principles and practices, but they have some important aspects in common. Both are holistic in approach,treating the whole patient, not the affected organs only; focusing on stimulating the intrinsic life principle to bring order, and on homeostasis and balance in the organism. In therapeutics, they may advantageously be applied as adjuvant to each other, producing synergistic effects.

To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.

AIM To understand the agreement, precision, and accuracy between other estimated glomerular filtration rate (eGFR) equations and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C equation (EPI_Cr_CysC). MATERIALS AND METHODS We conducted a cross-sectional study of 1,913 CKD patients. The eGFRs were calculated separately by creatinine clearance rate and Cockcroft-Gault equation corrected for standard body surface area (Ccr_BSA and eCcr_BSA); CKD-EPI creatinine equation (EPI_Cr); CKD-EPI cystatin C equation (EPI_CysC); EPI_Cr_CysC equation; Modification of Diet in Renal Disease (MDRD) Study equation with standardized serum creatinine; and full-age spectrum creatinine equation (FAS). The EPI_Cr_CysC equation was used as the reference. RESULTS When compared with the EPI_Cr_CysC equation, the EPI_Cr equation achieved the highest agreement in eGFRs (Lin's concordance correlation coefficient = 0.936, 95% confidence interval (CI) = 0.930, 0.941). eCcr_BSA and EPI_Cr equations achieved the first and second highest percentage agreement in the accurate classification of CKD stage (72.55 vs. 71.25%). The MDRD equation had minimal bias and was closely followed by the EPI_Cr equation (median difference = -1.3, 95% CI = -2.0, -0.8 vs. median difference = 2.5, 95% CI = 1.7, 3.3 mL/min/1.73m2). The EPI_CysC and EPI_Cr equations achieved the first and second highest precision (interquartile range (IQR) of the difference = 12.2, 95% CI = 11.6, 12.9 vs. IQR of the difference = 15.5, 95% CI = 14.7, 16.3 mL/min/1.73m2). The EPI_Cr and MDRD equations performed similarly and both had the highest accuracy at 30% (1 - P30 = 18.6, 95% CI = 16.9, 20.4 vs. 1 - P30 = 18.6, 95% CI = 16.8, 20.3%). CONCLUSION For assessment of renal function, the EPI_Cr equation performed the best and remained an acceptable alternative to the EPI_Cr_CysC equation in the absence of cystatin C. .

ObjectiveTo determine the prognostic values of histopathologic classification of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and other clinical and laboratory features at the time of presentation on renal and patient survival associated with myeloperoxidase-ANCA-associated glomerulonephritis (MPO-ANCA-GN).MethodsA total of 112 patients diagnosed with MPO-ANCA-GN from October 2005 to December 2018 were enrolled. The baseline clinical characteristics, renal histopathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed.ResultsAll 112 patients underwent renal biopsy. Disease in 32 patients was classified as focal, 26 as mixed, 29 as crescentic, and 25 as sclerotic. Over a median follow-up period of 41.5 months, there were 44 patients dialysis-dependent. The renal survival rate was significantly higher in the focal group than the other groups (p < 0.001) and significantly lower in the sclerotic group (p < 0.05). In addition, disease histopathologically classified as sclerotic (p = 0.044), high serum creatinine level (≥320 μmol/L, p < 0.001), low albumin (p = 0.024) and hemoglobin level (p = 0.044) were associated with a greater risk of ESRD. After follow-up, 70 (62.5%) of 112 patients survived. Old age (≥60 years, p = 0.018) and low serum albumin (p = 0.006) was significant risk factor for patient survival.ConclusionAmong patients with MPO-ANCA-GN, those with poor renal function, disease histopathologically classified as sclerotic, and lower albumin and hemoglobin levels were risk factors for ESRD, while older age and low serum albumin level were associated with a greater risk for all-cause mortality.

Background: An early net ultrafiltration (NUF) rate may be associated with prognosis in patients receiving continuous kidney replacement therapy (CKRT). In this study, we tested whether high or low early NUF rates in patients treated with CKRT were associated with increased mortality.Methods: We conducted a retrospective, observational study among all patients in the Medical Information Mart for Intensive Care IV database who received CKRT for more than 24 hours within 14 days after intensive care unit admission. We defined the early (initial 48 hours) NUF rate as the amount of fluid removal per hour adjusted by the patients’ weight and took it as a classified variable (low rate: < 1.6, moderate rate: 1.6–3.1 and high rate: > 3.1 mL/kg/h). The association between 28-day mortality and the NUF rate was analyzed by logistic regression and mediation analyses. Results: A total of 911 patients were included in our study. The median NUF rate was 2.71 (interquartile range 1.90–3.86) mL/kg/h and the 28-day mortality was 40.1%. Compared with the moderate NUF rate, the low NUF rate (adjusted odds ratio 1.56, 95% CI 1.04–2.35, p = 0.032) and high NUF rate (adjusted odds ratio 1.43, 95% CI 1.02–2.01, p = 0.040) were associated with higher 28-day mortality. The putative effect of a low or high NUF rate on 28-day mortality was possibly direct [adjusted average direct effects (ADE) 1.03, p = 0.096 for a low NUF rate; adjusted ADE 0.92, p = 0.064 for a high NUF rate], and also mediated by effects of the NUF rate on fluid balance during the same period [adjusted average causal mediation effects (ACME) 0.96, p = 0.010 for a low NUF rate; adjusted ACME 0.99, p = 0.042 for a high NUF rate]. Moreover, we found an increase trend in the NUF rate corresponding to the lowest mortality when fluid input increased. Conclusion: Compared with NUF rates between 1.6–3.1 mL/kg/h in the first 48 hours of CKRT, NUF rates > 3.1 mL/kg/h and < 1.6 mL/kg/h were associated with higher mortality.

Electroacupuncture (EA) is a promising clinical approach to treating posttraumatic stress disorder (PTSD), yet the mechanisms whereby EA can alleviate anxiety and other PTSD symptoms have yet to be clarified. In the present report, rats underwent EA for 14 consecutive days following modified single prolonged stress (MSPS) exposure. These animals were then evaluated in open field and elevated plus maze tests (OFT and EPM), while Fos immunohistochemical staining was performed to assess ventromedial prefrontal cortex (vmPFC) functional activation. In addition, an extracellular recording and stimulation system was used to analyze vmPFC inputs into the ventral tegmental area (VTA) in these rats. Temporary vmPFC inactivation was further performed to assess whether this was sufficient to reverse the anxiolytic effects of EA. Overall, rats that underwent EA treatment spent more time in the central region (OFT) and the open arm (EPM) relative to MSPS model animals (P < 0.05). These MSPS model animals also exhibited significantly fewer activated Fos-positive nuclei in the vmPFC following behavioral testing, while EA was associated with a significant relative increase in c-Fos expression in this region. The transient inactivation of the vmPFC was sufficient to reverse the effects of EA treatment on anxiety-like behaviors in MSPS model rats. MSPS and SEA rats exhibiting no differences in bursting activity between baseline and vmPFC stimulation, whereas bursting activity rose relative to baseline upon ventral mPFC stimulation in EA treated and control rats. Together, these findings indicate that the vmPFC and its inputs into the VTA are functionally linked to the anxiolytic activity of EA, implicating this pathway in the EA-mediated treatment of PTSD.

BackgroundImmune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy.MethodsWe carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types.ResultsNinety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3–5 RAEs, acute kidney injury (AKI), and grade 3–5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29–0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02–2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses.ConclusionsAmong ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3–5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3–5 AKI.Systematic Review RegistrationPROSPERO, identifier CRD42020197039.

Abnormal blood pressure variability (BPV) is associated with various organ injuries, high risk of cardio-cerebrovascular events and mortality. To investigate the association between mean perfusion pressure variability (MPPV) and mortality in critically ill patients admitted to the Intensive Care Unit (ICU), we analyzed data stored in the eICU-CRD database. MPPV was measured as the standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and variation independent of the mean (VIM) of the first 24 hours MPP data within the first 72 hours in the first ICU stay. A total of 6049 patients were included. Apart from SD, survivors had significantly lower MPPV in ARV, CV but higher VIM compared with non-survivors. After accounting for confounders, highest MPPV in decile using four measurements were associated with increased risk of hospital mortality compared with those in the fifth and sixth decile. In addition, lowest MPPV with dimension (mmHg) in decile also correlated to an increase in the risk of hospital mortality compared with the fifth and sixth decile. These relationships remained remarkable in the sensitive analyses. Increased MPPV and decreased MPPV with dimension were associated with short-term mortality in critically ill patients.

Introduction: Acute kidney injury has been identified as a common complication of cardiac surgery. To date, the effect of the time interval from coronary angiography to cardiac surgery on postoperative acute kidney injury is still controversial. The aim of this study was to investigate the relationship between the timing of coronary angiography and cardiac surgery associated acute kidney injury.Methods: Eight hundred thirteen patients who underwent coronary angiography and cardiac surgery successively from January 2017 to December 2018 were included in this retrospective cohort study. We applied multivariate logistic regression, propensity score analysis, and subgroup analysis to evaluate the association between the time interval and postoperative acute kidney injury incidence and prognosis. Meta-analysis was conducted to verify the results.Results: The overall incidence of the cardiac surgery associated acute kidney injury was 28.8%. Age (OR = 1.046, 95%CI: 1.017–1.075), cardiopulmonary bypass (OR = 3.439, 95%CI: 1.316–8.986) and diabetes (OR = 2.522, 95%CI: 1.439–4.417) were found to be independent risk factors of postoperative acute kidney injury in multivariate logistic regression and propensity score analysis. Undergoing cardiac surgery within 7 days after coronary angiography was not associated with increased incidence of postoperative acute kidney injury or worse prognosis. Meta-analysis obtained consistent results.Conclusions: The time interval shorter than 7 days had no influence on cardiac surgery associated acute kidney injury incidence and prognosis. The decision of delaying the surgery should be made after comprehensive evaluation of the patient.

Background: The optimal perfusion pressure target for acute kidney injury (AKI) in critically ill patients remains uncertain. We investigated the association between mean perfusion pressure (MPP) and AKI among critically ill patients and estimated its optimal range.Methods: We analyzed data stored in the Medical Information Mart for Intensive Care (MIMIC) -III, eICU Collaborative Research Database (eICU-CRD), and MIMIC-IV databases. Critically ill patients receiving invasive measurements of MPP for at least 12 hours within the first 24 hours of ICU stay were included. The exposure of interest was the time-weighted average MPP (TWA-MPP) in the first 24 hours. The primary outcome was the incidence of AKI in the next 48 hours. Results: We enrolled 7,992, 8,604, and 6,730 patients from the MIMIC-III, eICU-CRD, and MIMIC-IV databases, respectively. TWA-MPP had higher areas under the curve than mean arterial pressure in predicting AKI in the next 48 hours (0.63 vs 0.57, 0.62 vs 0.58, and 0.64 vs 0.58 in three databases, all p < 0.001). We observed the lowest adjusted risk of AKI when TWA-MPP above 72, 65, and 69 mmHg in the MIMIC-III, eICU-CRD, and MIMIC-IV databases, respectively. Pooled analyses indicated that per 10% increase of proportion of MPP above 65 mmHg was associated with decreased incidence of AKI (adjusted odds ratio = 0.93, 95% confidence interval = 0.92–0.94, p < 0.001). Furthermore, pooled analyses showed that the lowest risk of new-onset, persistence, and progression of AKI was estimated when TWA-MPP above 74, 70 and 65 mmHg, respectively. Conclusions: MPP outperformed mean arterial pressure as a perfusion predictor of AKI. MPP of 65 mmHg or higher may be the optimal target for managing AKI in critically ill patients. The target rises to higher when reversing or preventing AKI.

Recently, the Klotho protein (Klotho) has received substantial attention as protective factor against cardiovascular complications of chronic kidney disease (CKD). However, the direct effect and mechanism of Klotho on endothelial cells injury are not well‐known. In this study, we incubated human vein umbilical endothelial cells (HUVECs) with uremic toxin indoxyl sulfate (IS) to mimic CKD internal environment and investigated the direct effect of Klotho on the HUVECs injury induced by IS and to explore the mechanism in this process. We found IS inhibited cell viability, increased endoplasmic reticulum stress, and mediated apoptosis of HUVECs. Treatment with Klotho significantly attenuated IS‐induced above effects. Furthermore, Klotho alleviated the IS toxic effect on HUVECs via promoting AMP‐activated protein kinase (AMPK) α1 phosphorylation instead of directly upregulating AMPKα1, which could be partly blocked by AMPK pathway inhibitor‐Compound C. In addition, Klotho also inhibited intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) expression induced by IS. Altogether, these results indicated that Klotho can protect HUVECs from IS‐induced injury by alleviating AMPKα1‐mediated endoplasmic reticulum stress., Indoxyl sulfate (IS) injured human vein umbilical endothelial cells (HUVECs) and increased endoplasmic reticulum stress and mediated apoptosis of HUVECs. Klotho attenuated IS‐induced above effects via promoting AMP‐activated protein kinase (AMPK) α1 phosphorylation instead of directly upregulating AMPKα1.

OBJECTIVE To determine the prognostic values of clinical and laboratory features at the time of presentation on renal function and survival of patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. (MPO-ANCA GN). MATERIALS AND METHODS A total of 119 patients (52 males and 67 females) with MPO-ANCA GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2010 to April 2018 were enrolled. The baseline clinical characteristics, renal biopsy pathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed. RESULTS Among these 119 patients, the median serum creatinine at diagnosis was 354.30 (range, 216.10 - 637.30) mmol/L and the median estimated glomerular filtration rate (eGFR) was 14.78 (range, 7.23 - 29.21) mL/min. In total, 58 (48.7%) patients received initial renal replacement therapy (RRT). During a median follow-up duration of 32 (range, 3 - 113) months, 57 (47.9%) patients progressed to end-stage renal disease (ESRD). Initial renal function status (i.e., initial RRT, serum creatinine, and eGFR) (p < 0.001) and hemoglobin level (p = 0.027) were significant risk factors for renal survival. During the follow-up, 69 (57.6%) of 119 patients survived. Age (p = 0.009) and urine red blood cell count (p = 0.012) were predictive of patient survival. CONCLUSION Among patients with MPO-ANCA GN, poor renal function and lower hemoglobin level were predictive of ESRD, while older age and higher urinary red blood cell count were associated with a higher risk for all-cause mortality.

The aim of this study was to investigate the effect of 10.6-μm laser moxibustion and electroacupuncture in 5-fluorouracil (5-Fu)-induced diarrhea model rats. Forty-eight Sprague Dawley rats were randomly divided into 4 groups: a normal group, model group, 10.6-μm laser moxibustion (LM) group, and electroacupuncture (EA) group. Diarrhea was induced by 5-Fu (50 mg/kg) injection in 36 rats; the LM and EA groups received treatment at acupoint ST36 (Zusanli) on hind limbs once a day for 6 days. 5-Fu injection caused body weight decline and diarrhea. From the 5th to 7th day, the LM group showed higher body weights than the model group (P < 0.05). On the 6th day, diarrhea score of the LM group was better than that of the EA group (P < 0.05). Both scores of the LM group and EA group were better than that of model group (P < 0.05). The LM group and EA group both had better intestine pathological scores and lower endotoxin (ET) and diamine oxide (DAO) activity than the model group (P < 0.01). The LM group got better pathological scores than the EA group (P < 0.01). Ultramicroscopic structures of the model group showed severe damage while the LM group and EA group remained good in their small intestines. The model group had obviously decreased occludin protein in intestine tissues than the control group (P < 0.01), while occludin expressions in the LM group and EA group were both obviously increased compared with the model group (P < 0.01). LM and EA treatment on ST36 could alleviate damage to intestinal barrier function and alleviate diarrhea caused by 5-Fu.

The cuticular wax of Korla pear stored under different relative humidity (0 ± 1 ℃, 50–55%, 70–75% and 90–95%) was examined in terms of total wax content, chemical composition and crystal morphology. The cuticular wax was composed of alkanes, olefins, fatty acids, alcohols, aldehydes, esters and terpenoids. High humidity maintained the content of total wax, alkanes and aldehydes at sufficient levels, especially C29 alkane and C18 aldehyde, which could positively regulate the quality of the pear fruits. Cuticular wax contributes to the capacity of preserving water, maintaining cell wall and delaying senescence. Scanning electron microscopy showed that wax crystals appeared as numerous platelets with irregular ovate crystals, high humidity delayed the transformation of wax structure. Taken together, high humidity delayed the ripening and aging by effectively maintaining wax, which was essential for postharvest storage and provide a reference for the production of synthetic wax for Korla pear fruits.

Traditional Indian medicine or Ayurveda (阿育吠陀) and Traditional Chinese Medicine remain the most ancient yet living traditions. These are the two great traditional medicines with rich philosophical, experiential, and experimental basis. Both the systems have been developed and enriched by thousands of years of practices, observations, and experiences. As India and China are neighbors, some exchange of medical ideas and practices might have occurred between the two nations since ancient times. Therefore, when the two traditional medicines are examined closely, many similarities become apparent in the theories and practices along with individual differences.

Purpose: Accurate preoperative parathyroid localization is important for successful parathyroidectomy (PTX). The aim of our study was to investigate whether SPECT/CT has enhanced effect in preoperative localization of parathyroids. Methods: In our retrospective cohort study, we evaluated the effects of technetium-99m methoxyisobutylisonitrile-single-photon emission computed tomography/computed tomography (99mTc-MIBI SPECT/CT) on preoperative parathyroid localization for 645 secondary hyperparathyroidism (SHPT) patients. Among them, 569 successful PTX patients were divided into group A (received 99mTc-MIBI scintigraphy, n = 175) and group B (received 99mTc-MIBI scintigraphy and SPECT/CT imaging, n = 394). Sensitivity, specificity, and consistency of two imaging methods in preoperative localization of parathyroids were compared. Results: Overall sensitivity and consistency were higher in group B, while there was no difference in specificity between the two groups. In group A, the sensitivity of 99mTc-MIBI was 50.00%, 77.11%, 61.76%, and 76.54% in the right upper gland (RU), right lower gland (RL), left upper gland (LU), and left lower gland (LL) subgroups, while the consistency was 52.00%, 76.57%, 61.71%, and 75.43%, respectively. In group B, the sensitivity of 99mTc-MIBI with SPECT/CT was 69.39%, 90.03%, 78.07%, and 84.27%, and the consistency was 69.54%, 88.32%, 78.43%, and 84.26%, respectively. The sensitivity and consistency in lower glands were higher than in upper glands in both groups. Sensitivity for eutopic parathyroid was higher in group B, while there was no difference for ectopic parathyroid. Conclusions: 99mTc-MIBI SPECT/CT can increase the sensitivity and consistency of preoperative localization of eutopic parathyroid glands, and it can accurately locate ectopic parathyroid without sensitivity improvement.

BACKGROUND The predictive value of Doppler-based renal resistive index (RRI) for acute kidney injury (AKI) has not been fully elucidated. The present meta-analysis was carried out to disclose the correlation between AKI and RRI, and to investigate the predictive value of RRI for the onset of AKI and its recovery. MATERIALS AND METHODS We searched PubMed, Embase, and Cochrane Library databases from inception to March 2019. The weighted mean difference (WMD) with a 95% confidence interval (CI) was used to assess the difference in RRIs between AKI and non-AKI patients. Moreover, the sensitivity and specificity were calculated, and summary receiver operating characteristic (SROC) curves were constructed. Meta-Disc and STATA were used for all statistical analyses. RESULTS A total of 20 studies (14 for prediction of the onset of AKI and 6 for prediction of AKI short-term non-recovery) were included in our meta-analysis. The values of RRI (WMD = 0.07; 95% CI: 0.05 - 0.09; p < 0.0001) were significantly higher in AKI patients compared with non-AKI patients. The overall sensitivity and specificity of RRI for prediction of the onset of AKI were 72% (95% CI, 64 - 80%) and 79% (95% CI, 71 - 85%), respectively. As for prediction of AKI short-term non-recovery, the pooled sensitivity was 81% (95% CI: 64 - 91), and the pooled specificity was 80% (95% CI: 72 - 85). For the onset of AKI, the best predictive performance was observed for the RRI measured immediately after major surgery, and a cut-off value ≥ 0.715 also achieved superior predictive value. CONCLUSION This study showed that the elevation of RRI may be related to the progression of AKI, and RRI could have good overall predictive value for the onset of AKI and its short-term non-recovery. Further studies in different clinical settings and patient groups are warranted before it could be widely used in clinical practice.

Vascular calcification (VC) is a strong predictor of cardiovascular mortality and overall mortality in patients with chronic kidney disease (CKD); however, the molecular mechanisms underlying VC have yet to be elucidated. Here, we report the role of the deubiquitinating enzyme BRCC36 in the process of VC in CKD. We established an in vitro VC model of vascular smooth muscle cells (VSMCs) and an adenine-induced CKD mouse model. The expression of BRCC36 was significantly decreased in both the in vivo and in vitro VC models. Alizarin red staining and calcium content assays showed that BRCC36 overexpression reduced calcium deposition in the presence of calcifying medium, while the contractile protein α-smooth muscle actin (α-SMA) was upregulated and phosphorylated β-catenin was downregulated. Cell immunofluorescence showed that BRCC36 overexpression also reduced the expression of phosphorylated β-catenin in the nucleus in the presence of calcifying medium. In addition, coimmunoprecipitation showed that BRCC36 can bind to β-catenin. These results suggest that BRCC36 can interact with β-catenin, the main effector protein of the Wnt/β-catenin pathway, inhibiting the phosphorylation of β-catenin and negatively regulating the cell signalling pathway, thereby inhibiting VC. This may provide new insights into the molecular mechanisms of VC in the context of CKD.

Acute kidney injury (AKI) is a common disease, but diagnosis is usually delayed or missed in hospitalized patients. The aim of this study was to investigate the impact of under-recognition of AKI (beyond 3 days after AKI onset) on short-time prognosis. Of 785 patients with under-recognition of AKI and 616 patients with timely-recognition of AKI were propensity matched in a 1:1 ratio. The two groups, with a total of 482 matched patients (241:241), were comparable in baseline covariates. Under-recognition of AKI was not associated with 30-day all-cause mortality in the logistic regression model with covariate adjustment (OR = 1.01, 95% CI = 0.62–1.64, p = 0.967). Sensitivity analyses and subgroup analyses also proved the association. There were also no significant differences in causes of 30-day mortality, in-hospital mortality, recovery of renal function at discharge, length of hospital stay, length of intensive care unit stay or hospitalization costs between the two groups, although timely-recognition group had more chance of renal consult and a little more interventions for AKI. In conclusion, under-recognition of AKI may not be associated with poor short-term outcomes of adult hospitalized patients via these propensity-score-matched analyses.

Fibroblastic growth factor 23 (FGF23) is a hormone secreted primarily by bone. FGF23 is elevated in the serum of chronic kidney disease (CKD) patients, but the exact mechanism is not well known. Klotho is identified as an aging suppressor, which is mainly expressed in the kidney, and the level of soluble Klotho is negatively associated with FGF23 in CKD. The aim of this study was to investigate the effect and possible mechanism of Klotho on FGF23 synthesis in osteoblast-like UMR-106 cells. UMR-106 cells were divided into five groups: (i) control group; (ii) β-glycerophosphate (β-GP) group; (iii) β-GP + Klotho group; (iv) β-GP+ lithium chloride (LiCl, a Wnt/β-catenin pathway agonist) group; and (v) β-GP + Klotho + LiCl group. Subsequently, UMR-106 cells were cultured for 72 h, and the expression of FGF23, P-glycogen synthase kinase-3β (P-GSK-3β), and glycogen synthase kinase-3β(GSK-3β) were measured with Western blot analysis. The mRNA levels of FGF23 and the Wnt/β-catenin pathway target gene c-myc were determined with RT-qPCR. The results showed that β-GP induced increased expression of FGF23 mRNA and protein. Compared with the β-GP group, expression of FGF23 mRNA and protein expression were downregulated in the β-GP + Klotho group. In addition, β-GP induced increased expression of P-GSK-3β/GSK-3β and c-myc, which were all downregulated in the β-GP + Klotho group. Moreover, the expression of FGF23, P-GSK-3β/GSK-3β, and c-myc mRNA were upregulated when treated with LiCl. These results demonstrate that soluble Klotho suppresses FGF23 synthesis in osteoblast-like UMR-106 cells. The mechanism of this suppression may be partially through the inhibition of the Wnt/β-catenin pathway.

The aim of this study is to investigate the association between body composition, measured by bioelectrical impedance analysis, and outcomes in patients with acute kidney injury (AKI) receiving kidney replacement therapy (KRT).Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed by body composition analysis before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors included lean tissue index (LTI), fat tissue index, and body cell mass index (BCMI). The association between all-cause mortality and predictors was analyzed using Cox regression.A total of 152 patients were included in this study, with a 28-day mortality of 46.7% and 1-year mortality of 60.5%. LTI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.66, P .001) and BCMI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.67, P .001) on day 7 after initiation of KRT, rather than before KRT, were associated with mortality during follow-up. LTI and BCMI before KRT were associated with 28-day mortality rather than 1-year mortality.LTI and BCMI before KRT were associated with short-term prognosis, and those on day 7 after KRT initiation were associated with intermediate mortality in patients with AKI requiring KRT.

Long‐term peritoneal dialysis is accompanied by functional and histopathological alterations in the peritoneal membrane. In the long process of peritoneal dialysis, high‐glucose peritoneal dialysis solution (HGPDS) will aggravate the peritoneal fibrosis, leading to decreased effectiveness of peritoneal dialysis and ultrafiltration failure. In this study, we found that the coincidence of elevated TGF‐β1 expression, autophagy, apoptosis and fibrosis in peritoneal membrane from patients with peritoneal dialysis. The peritoneal membranes from patients were performed with immunocytochemistry and transmission electron microscopy. Human peritoneal mesothelial cells were treated with 1.5%, 2.5% and 4.25% HGPDS for 24 hrs; Human peritoneal mesothelial cells pre‐treated with TGF‐β1 (10 ng/ml) or transfected with siRNA Beclin1 were treated with 4.25% HGPDS or vehicle for 24 hrs. We further detected the production of TGF‐β1, activation of TGF‐β1/Smad2/3 signalling, induction of autophagy, EMT, fibrosis and apoptosis. We also explored whether autophagy inhibition by siRNA targeting Beclin 1 reduces EMT, fibrosis and apoptosis in human peritoneal mesothelial cells. HGPDS increased TGF‐β1 production, activated TGF‐β1/Smad2/3 signalling and induced autophagy, fibrosis and apoptosis hallmarks in human peritoneal mesothelial cells; HGPDS‐induced Beclin 1‐dependent autophagy in human peritoneal mesothelial cells; Autophagy inhibition by siRNA Beclin 1 reduced EMT, fibrosis and apoptosis in human peritoneal mesothelial cells. Taken all together, these studies are expected to open a new avenue in the understanding of peritoneal fibrosis, which may guide us to explore the compounds targeting autophagy and achieve the therapeutic improvement of PD.

Glucocorticoids (GCs) are commonly used in the treatment of nephrotic syndrome. However, high doses and long periods of GC therapy can result in severe side effects. The present study aimed to selectively deliver albumin‑methylprednisolone (MP) nanoparticles towards glomerular podocytes, which highly express the specific neonatal Fc receptor (FcRn) of albumin. Bovine serum albumin (BSA) was labeled with a fluorescent dye and linked with modified MP via an amide bond. The outcome nanoparticle named BSA633‑MP showed a uniform size with a diameter of approximately 10 nm and contained 12 drug molecules on average. The nanoconjugates were found to be stable at pH 7.4 and acid‑sensitive at pH 4.0, with approximately 72% release of the MP drug after 48 h of incubation. The nanoparticle demonstrated a 36‑fold uptake in receptor‑specific cellular delivery in the FcRn‑expressing human podocytes compared to the uptake in the non-FcRn-expressing control cells. Co‑localization further confirmed that uptake of the nanoconjugates involved receptor‑mediated endocytosis followed by lysosome associated transportation. In vitro cellular experiments indicated that the BSA633‑MP ameliorated puromycin aminonucleoside‑induced podocyte apoptosis. Moreover, in vivo fluorescence molecular imaging showed that BSA633-MP was mainly accumulated in the liver and kidney after intravenous dosing for 24 h. Collectively, this study may provide an approach for the effective and safe therapy of nephrotic syndrome.

// Chuanyan Zhao 1, * , Zhuyun Chen 1, * , Jia Qi 2 , Suyan Duan 1 , Zhimin Huang 1 , Chengning Zhang 1 , Lin Wu 1 , Ming Zeng 1 , Bo Zhang 1 , Ningning Wang 1 , Huijuan Mao 1 , Aihua Zhang 3, 4 , Changying Xing 1 , Yanggang Yuan 1 1 Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China 2 Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China 3 Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China 4 Institute of Pediatrics, Nanjing Medical University, Nanjing, China * These authors are contributed equally to this work Correspondence to: Yanggang Yuan, email: ygyuan@njmu.edu.cn Changying Xing, email: cyxing1962@163.com Keywords: Drp1, mitophagy, mitochondrial dysfunction, mitochondrial fission, cisplatin Received: July 10, 2016 Accepted: February 07, 2017 Published: February 18, 2017 ABSTRACT Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients. There is increasing evidence that mitochondrial dysfunction plays an important role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is carried out by mitophagy. Although mitophagy is considered of particular importance in protecting against AKI, little is known of the precise role of mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity. Also, evidence that activation of mitophagy improved mitochondrial function is lacking. Furthermore, several evidences have shown that mitochondrial fission coordinates with mitophagy. The aim of this study was to investigate whether activation of mitophagy protects against mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment. The effect of mitochondrial fission on mitophagy was also investigated. In cultured human renal proximal tubular cells, we observed that 3-methyladenine, a pharmacological inhibitor of autophagy, blocked mitophagy and exacerbated cisplatin-induced mitochondrial dysfunction and cells injury. In contrast, autophagy activator rapamycin enhanced mitophagy and protected against the harmful effects of cisplatin on mitochondrial function and cells viability. Suppression of mitochondrial fission by knockdown of its main regulator dynamin-related protein-1 (Drp1) decreased cisplatin-induced mitophagy. Meanwhile, Drp1 suppression protected against cisplatin-induced cells injury by inhibiting mitochondrial dysfunction. Our results provide evidence that Drp1-depedent mitophagy has potential as renoprotective targets for the treatment of cisplatin-induced AKI.

Background: Secondary hyperthyroidism (SHPT) is a common complication in chronic kidney disease patients undergoing peritoneal dialysis. It develops as a result of distortions in the regulation of calcium, phosphorus and parathyroid hormone (PTH). SHPT increases with decreasing kidney function. Factors that affect the levels of calcium, phosphorus, and PTH include diet, residual renal function, peritoneal transport properties, and dialysate calcium concentration. Treatment options for SHPT include pharmaceutical and surgical removal of parathyroid glands. Although there are treatment options for kidney disease patients with SHPT, little improvement has been made in the overall outcome of the patients. Method: Here, we present that parathyroidectomy is a treatment option for patients with SHPT. A test group (peritoneal dialysis patients with SHPT who had surgery plus forearm transplantation) were compared with control group (normal peritoneal dialysis patients without surgery). In both groups, clinical, biochemical and haematological profile assessments were done. Results: The test group after surgery show improved clinical, biochemical and haematological profile comparing with the control (non-surgery) group. Conclusion: parathyroidectomy (PTX) is a reliable treatment option for patients with SHPT, which brings about improvement in the biochemical, haematological, physiological and clinical parameters as compared with peritoneal dialysis patients with secondary hyperthyroidism without parathyroidectomy plus forearm transplantation.

Objective. Coronary slow/no reflow is not rare after successfully undergoing primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI), and shock index (SI) is an important factor for adverse cardiovascular prognosis. In this study, we are to explore whether SI is associated with coronary slow/no reflow in patients with AMI following primary PCI. Methods. A total of 153 consecutive AMI patients undergoing primary PCI within 24 hours of symptom onset were included in this study. The participants were divided into normal flow group (n=124) and slow/no reflow group (n=29) according to cineangiograms recorded during the period of PCI. Cardiovascular risk factors, hematologic parameters, preoperative management of antithrombotic therapy, and baseline angiography were collected. Results. SI, plasma glucose, white blood cells (WBC) and neutrophil count, neutrophil to lymphocyte ratio (PLR), high sensitivity C-reactive protein (hs-CRP), probrain natriuretic peptide (pro-BNP), and Killip classification on admission and thrombus burden on initial angiography were significantly different between patients with and without slow/no reflow. Multivariate analysis revealed that SI≥0.66, thrombus burden, and plasma glucose on admission were independent predictors for coronary slow/no reflow. Preoperative management of tirofiban therapy improves initial thrombolysis in myocardial infarction (TIMI). However, it has no effect on prognosis of slow/no reflow. Conclusion. Our findings demonstrated that slow/no reflow in patients with AMI following primary PCI was more likely associated with SI≥0.66, thrombus burden, and plasma glucose on admission. SI as a predictor for coronary slow/no reflow should be further confirmed in the following more large-scale and prospective studies. The clinical registration number is ChiCTR1900024447.

BACKGROUND Fatigue is the most common symptom negatively affecting the quality of life of patients with cancer. The objective of the current study was to evaluate the preliminary efficacy and safety of 10.6‐μm infrared laser moxibustion for cancer‐related fatigue (CRF). METHODS The authors conducted a randomized, placebo‐controlled trial among 78 patients with cancer who were diagnosed with CRF. The group treated with infrared laser moxibustion received 10.6 μm of infrared laser moxibustion on the ST36 (bilateral), CV4, and CV6 acupoints. Each participant received a 20‐minute treatment session 3 times per week for 4 weeks. The sham group received the same treatment duration on the same acupoints, but without infrared laser output. The outcome was change in fatigue as measured by the Chinese version of the Brief Fatigue Inventory between groups at week 4 with additional evaluation at week 8 for durability of treatment effects. A mixed effects model was used to evaluate the difference in treatment effect over time. RESULTS Among those randomized, 61 patients (78%) completed the entire study. At the end of the intervention, the individuals in the group treated with the laser were found to have significantly less fatigue than those in the sham group (3.01 vs 4.40; P = .002). The improvement in fatigue persisted to week 8, favoring the group treated with laser moxibustion (3.03 vs 4.26; P = .006). Laser moxibustion was safe, with 3 cases of mild local erythema that resolved without medical intervention reported. CONCLUSIONS Infrared laser moxibustion appeared to be safe and efficacious for improving CRF in a Chinese patient population. Larger studies in more racial/ethnically diverse populations are needed to confirm the benefit of this technique for fatigue in patients with cancer. Cancer 2016;122:3667‐72. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes., The current study is a randomized, double‐blind, placebo‐controlled trial of infrared laser moxibustion for the treatment of cancer‐related fatigue. Infrared moxibustion appears to be a promising new therapy for this complication.

It is unclear whether clinical courses of hungry bone syndrome (HBS) after parathyroidectomy (PTX) in peritoneal dialysis (PD) and hemodialysis (HD) patients are different. The present study aimed to investigate the possible differences of postoperative hypocalcemia and hyperkalemia between PD and HD patients. We performed retrospectively 29 PD patients as the PD group and 169 HD patients as the HD group undergoing successful total PTX with autotransplantation. Calcium supplement after surgery was recorded. Higher levels of serum potassium during and immediately after surgery were recorded as K+d0. K+d3 was recorded as peak pre-dialysis serum potassium level 3 days post-surgery. There were 157 (92.90%) patients in HD group and 22 (75.86%) patients in PD group suffered from HBS after surgery, with significant difference between the groups (P = 0.004). Patients in PD group had significantly shorter intravenous calcium supplement duration (P = 0.037) and significantly smaller intravenous calcium supplement dosage (P = 0.042) and total calcium supplement dosage during hospitalization (P = 0.012) than patients in HD group. The levels of serum K+d0 (P

The Src homology and collagen A (ShcA) adaptor protein that binds to tyrosine kinase receptors. ShcA plays a role in insulin signaling, stress resistance and energy metabolism. The 66-kDa Src homology 2 domain-containing protein (p66shc) belongs to the ShcA family and has been associated with reactive oxygen species (ROS); increased ROS is involved in the pathology of lupus nephritis (LN). However, whether ShcA can act as a biomarker for oxidative injury in LN is unknown. This study is aimed to investigate the ShcA expression in kidney tissues from patients presenting with LN and the association between ShcA expression and clinical parameters. Renal biopsy tissues were obtained from 62 LN, 20 primary membranous nephropathy (MN) and 10 other secondary MN patients. ShcA was measured by immunofluorescence. The expression of ShcA in the membranous lupus nephritis (class V) group showed a higher trend but there were no significant differences compared with pure mesangial disease (class II) and proliferative (Class III/IV) lupus nephritis. ShcA deposits were negative in primary and other secondary MN. ShcA might act as a new biomarker and a diagnostic tool to identify membranous lupus nephritis with other MN.

PURPOSE: Fatigue is the most common and distressing symptom experienced by cancer survivors. This study sought to determine the prevalence and risk factors for fatigue among breast cancer (BC) survivors receiving aromatase inhibitors (AIs). MATERIAL AND METHODS: We conducted a cross-sectional survey study among postmenopausal women with stage 0 to III BC receiving adjuvant AI therapy at the outpatient breast oncology clinic of a large university hospital. Participants with a score ≥4 on the “worst fatigue” item of the Brief Fatigue Inventory (BFI) were classified as having moderate or severe fatigue. Multivariate logistic regression analyses were performed to evaluate risk factors. RESULTS: Among 1,103 participants, 616 (55.8%) had moderate or severe fatigue. In the multivariate logistic regression model, women younger than 55 years were significantly more likely to report moderate-severe fatigue than women older than 65 years (adjusted odds ratio (AOR), 1.58, 95% confidence interval (CI) 1.07–2.35; p=0.023). Compared to women with high school or less education, women with college or more education were significantly more likely to report moderate-severe fatigue (AOR, 1.40, 95% CI 1.02–1.91; p=0.037). Increasing body mass index (BMI) was significantly associated with increased risk of experiencing moderate-severe fatigue (overweight: AOR, 1.37, 95% CI 1.01–1.84; p=0.042; obesity: AOR, 2.08, 95% CI 1.53–2.81; p

Background: In chronic kidney disease (CKD) patients, decreased heart rate variability (HRV) reflects impaired cardiac automatic nervous function and high risk of cardiovascular disease (CVD). Lower HRV in patients with severe secondary hyperparathyroidism (SHPT), a clinical manifestation of CKD-mineral and bone disorder (CKD-MBD), could be reversed by parathyroidectomy (PTX). It has been proved that leptin interacts with the autonomic nervous function. However, the associations between leptin and HRV in CKD patients and their longitudinal changes in SHPT patients after PTX are still unknown. Methods: This was a cross-sectional study including 141 stage 5 CKD patients, and a prospective study in 36 severe SHPT patients with PTX. HRV was measured by Holter and serum leptin was measured by ELISA. Serum leptin levels were adjusted for body mass index (BMI) and transformed using natural logarithm (lnleptin/BMI). Results: With a gradient of lnleptin/BMI across quartiles from Q1 to Q4 in CKD patients, HRV indices showed no differences among quartiles. Patients in Q1 group had higher mean 24 h heart rates, and lower ln(very low frequency) (lnVLF) than other quartiles, although there were no statistically significant difference. In multivariate stepwise regression, serum leptin/BMI was an independent predictor for low frequency/high frequency. HRV indices and lnleptin/BMI levels were increased in severe SHPT patients after PTX. Compared to other quartiles, SHPT patients in Q1 group had larger improvement of lnVLF after PTX. Conclusion: Circulating leptin levels may be a novel treatment target to reduce CVD risk in advanced CKD-MBD patients.

Podocytes play an important role in the pathogenesis and progression of glomerulosclerosis. Recent studies indicate that aldosterone/mineralocorticoid receptor (MR) is a major contributor of chronic kidney disease (CKD) progression. Aldosterone/MR induces glomerular podocyte injury, causing the disruption of the glomerular filtration barrier and proteinuria. The present study investigated the mechanisms by which aldosterone/MR mediated podocyte injury, focusing on the involvement of oxidative stress, endoplasmic reticulum (ER) stress, and autophagy. We observed that aldosterone/MR induced ER stress and podocyte injury both in vivo and in vitro. Blockade of ER stress significantly reduced aldosterone/MR-induced podocyte injury. In addition, we found that ER stress-induced podocyte injury was mediated by CCAAT/enhancer-binding protein (C/EBP) homologous protein (Chop). Interestingly, autophagy was also enhanced by aldosterone/MR. Pharmacological inhibition of autophagy resulted in increased apoptosis. Inhibition of ER stress significantly reduced aldosterone/MR-induced autophagy. In addition, the activation of ER stress increased the formation of autophagy, which protected podocytes from apoptosis. Moreover, we observed that the addition of ROS scavenger, N-acetyl cystein (NAC), blocked both ER stress and autophagy by aldosterone/MR. Collectively, these results suggest that oxidant stress-mediated aldosterone/MR-induced podocyte injury via activating ER stress, which then triggers both Chop-dependent apoptosis and autophagy to cope with the injury. These findings may guide us to therapeutic strategies for glomerular diseases.

The aim of the present study was to investigate the effect of the serum of patients with secondary hyperparathyroidism (SHPT) on endothelial cells and to examine the protective effect and the possible mechanism of Klotho. A total of three types of mixed serum from 15 patients with SHPT scheduled for parathyroidectomy, 10 chronic kidney disease (CKD) patients at stage 5 without SHPT and 15 healthy volunteers were collected. Initially, human umbilical vein endothelial cells (HUVECs) were incubated in vitro with the three types of serum and levels of proliferation were compared by assessing viable cell numbers with cell counting kit-8 (CCK-8). Subsequently, HUVECs were divided into three groups: Control group (healthy serum medium), SHPT group (SHPT serum) and Klotho treatment group (SHPT serum and Klotho). The proliferative and apoptotic levels of endothelial cells were evaluated by CCK-8 and flow cytometry, respectively. The levels of extracellular signal-regulated kinase (ERK1/2) and phosphorylated forms of ERK1/2 (p-ERK1/2) were detected using western blotting (with or without ERK1/2 inhibitor PD98059). The synthesis of nitric oxide (NO) was measured using the nitrate reduction method. The proliferation of HUVECs was inhibited by the serum from SHPT patients and CKD-5 patients without SHPT and the inhibitory effects of the SHPT serum were the most marked (P

Fibroblastic growth factor 23 (FGF23) is a hormone secreted primarily by bone. FGF23 is elevated in the serum of chronic kidney disease (CKD) patients, but the exact mechanism is not well known. Klotho is identified as an aging suppressor, which is mainly expressed in the kidney, and the level of soluble Klotho is negatively associated with FGF23 in CKD. The aim of this study was to investigate the effect and possible mechanism of Klotho on FGF23 synthesis in osteoblast-like UMR-106 cells. UMR-106 cells were divided into five groups: (i) control group; (ii) β-glycerophosphate (β-GP) group; (iii) β-GP + Klotho group; (iv) β-GP+ lithium chloride (LiCl, a Wnt/β-catenin pathway agonist) group; and (v) β-GP + Klotho + LiCl group. Subsequently, UMR-106 cells were cultured for 72 h, and the expression of FGF23, P-glycogen synthase kinase-3β (P-GSK-3β), and glycogen synthase kinase-3β(GSK-3β) were measured with Western blot analysis. The mRNA levels of FGF23 and the Wnt/β-catenin pathway target gene c-myc were determined with RT-qPCR. The results showed that β-GP induced increased expression of FGF23 mRNA and protein. Compared with the β-GP group, expression of FGF23 mRNA and protein expression were downregulated in the β-GP + Klotho group. In addition, β-GP induced increased expression of P-GSK-3β/GSK-3β and c-myc, which were all downregulated in the β-GP + Klotho group. Moreover, the expression of FGF23, P-GSK-3β/GSK-3β, and c-myc mRNA were upregulated when treated with LiCl. These results demonstrate that soluble Klotho suppresses FGF23 synthesis in osteoblast-like UMR-106 cells. The mechanism of this suppression may be partially through the inhibition of the Wnt/β-catenin pathway.

Background/Aims: To evaluate the long-term outcomes of Chinese patients with cardiac surgery-associated acute kidney injury (CSA-AKI). Methods: Patients who underwent cardiac surgery with a median 3-year follow-up were enrolled. The long-term survival rate and the incidence of chronic kidney disease (CKD) were recorded, and related risk factors were analyzed. Results: Of all 1,363 patients, 457 (33.5%) developed CSA-AKI. The AKI patients had a lower 3-year survival rate (88.8 vs. 97.2%, respectively, p < 0.001) and a higher incidence of CKD stages 3-5 (9.9 vs. 2.3%, respectively, p < 0.001) than the non-AKI patients. Cox regression analysis showed that AKI, atrial fibrillation, chronic cardiac insufficiency, longer surgical duration, respiratory failure after surgery, and longer mechanical ventilation time were associated with long-term mortality, while AKI, older age, and lower baseline kidney function were associated with incident CKD stages 3-5. Conclusion: CSA-AKI increased the risk of 3-year mortality and incident CKD stages 3-5.